Alzheimers disease may result from low-grade inflammation of the brain, and the characteristic amyloid may be a protective response. Epidemiological observation indicates that long-term oral administration of nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen to patients having rheumatoid arthritis results in reduced risk and delayed onset of Alzheimers disease. However, oral ibuprofen, flurbiprofen, and other NSAIDs are not an effective treatment. The NSAIDs may work as an Alzheimers preventive but not a treatment because the oral dose to the brain is too small, 1% to 2% of the total plasma concentration. The NSAID brain dose could be significantly increased by delivering the drug intranasally. Flurbiprofen would be preferable to ibuprofen because flurbiprofen has 12 times the potency of ibuprofen. The smaller nasal dose of flurbiprofen than ibuprofen could significantly increase patient compliance. Alzheimers disease starts in the entorhinal cortex, which is closely connected to the olfactory nerves, and spreads anatomically in a defined pattern. Therefore, a nasal NSAID would readily reach the region of the brain where it is most likely to be therapeutic.

A derangement of brain wound healing may cause some cases of Alzheimers disease. Wound healing, a highly complex process, has four stages: hemostasis, inflammation, repair, and remodeling. Hemostasis and the initial phases of inflammation in brain tissue are typical of all vascularized tissue, such as skin. However, distinct differences arise in brain tissue during the later stages of inflammation, repair, and remodeling, and closely parallel the changes of Alzheimers disease. Our hypothesis -- Alzheimers disease is brain wound healing gone awry at least in some cases -- could be tested by measuring progression with biomarkers for the four stages of wound healing in humans or appropriate animal models. Autopsy studies might be done. Chronic traumatic encephalopathy might also result from the brain wound healing process.